Azilsartan medoxomil is chemically, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-2-ethoxy-1-([2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl)-1H-benzimidazole-7-carboxylate and has the structural formula:

Azilsartan (INN, codenamed TAK-536) is an angiotensin II receptor antagonist used in the treatment of hypertension. It is marketed by Takeda Pharmaceuticals under the brand name EDARBI®.
Azilsartan acid and its process were disclosed in U.S. Pat. No. 5,243,054 (054 patent).
Azilsartan medoxomil and its potassium salt were disclosed in U.S. Pat. No. 7,157,584 (584 patent).
Polymorphism is defined as “the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice. Thus, in the strict sense, polymorphs are different crystalline structures of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules”. Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph. It is therefore important to investigate all solid forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Infrared spectrometry (IR).
Solvent medium and mode of crystallization play very important role in obtaining one polymorphic Form over the other.
Azilsartan medoxomil and its potassium salt can exist in different polymorphic Forms, which may differ from each other in terms of stability, physical properties, spectral data and methods of preparation.
Process for the preparation of azilsartan medoxomil was disclosed in the '584 patent. According to the patent, crystalline solid of azilsartan medoxomil was obtained by reacting 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid with 4-hydroxymethyl-5-methyl-1,3-dioxol-2-one in N,N-dimethylacetamide in the presence of p-toluenesulfonyl chloride, N,N-dimethylaminopyridine and potassium carbonate at low temperature to give solvate. The obtained solvate was crystallized in water and acetone to obtain azilsartan medoxomil. The crystalline azilsartan medoxomil obtained by the process of the prior art is herein after designated as azilsartan medoxomil crystalline Form I. The powdered x-ray diffractogram (PXRD) of azilsartan medoxomil crystalline Form I is shown in FIG. 2. Crystalline Form I of azilsartan medoxomil is characterized by peaks in the powder x-ray diffraction spectrum having 2θ angle positions at about 11.6, 13.3, 16.0, 20.3, 23.3, 23.5 and 24.1±0.2 degrees.
International patent application publication no. WO 2012/090043 disclosed crystalline Form J2, J3, J4, J5, J6, J7, J8, J9 and amorphous Form of azilsartan medoxomil.
An unpublished application, IN 2760/CHE/2012 assigned to Hetero Research Foundation discloses a crystalline Form II of azilsartan medoxomil potassium. The application also disclosed a crystalline Form II of azilsartan acid.
We have found a novel amorphous Form of azilsartan acid. The novel crystalline Form of azilsartan acid is stable, reproducible and so, suitable for pharmaceutical preparations.
We have also found novel crystalline Forms of azilsartan medoxomil. The novel crystalline Forms of azilsartan medoxomil are stable, reproducible and so, suitable for pharmaceutical preparations.
We have also found a novel amorphous Form of azilsartan medoxomil potassium. The novel amorphous Form of azilsartan medoxomil potassium is stable, reproducible and so, suitable for pharmaceutical preparations.
We have also found a novel process for the preparation of azilsartan medoxomil potassium crystalline Form II.
Thus, one object of the present invention is to provide a novel amorphous Form of azilsartan acid, process for its preparation and pharmaceutical compositions comprising it.
Another object of the present invention is to provide novel crystalline Forms of azilsartan medoxomil, processes for their preparation and pharmaceutical compositions comprising them.
Another object of the present invention is to provide a novel amorphous Form of azilsartan medoxomil potassium, process for its preparation and pharmaceutical compositions comprising it.
Another object of the present invention is to provide a novel process for the preparation of azilsartan medoxomil crystalline Form II.